Pemetrexed combined with paclitaxel: a dose-finding study evaluating three schedules in solid tumors.
The objectives of this phase I study were to determine the maximum tolerated dose (MTD), recommended phase II dose (RD), antitumor activity, safety, and pharmacokinetics of pemetrexed-paclitaxel combination. Patients (N = 95) with advanced solid tumors were assigned to three schedules (21-day cycles [q21d]). Starting doses for each schedule of pemetrexed and paclitaxel, respectively, were: (S1) 400 and 135 mg/m(2) on d1; (S2) 400 mg/m(2) d1 and 40 mg/m(2) d1 and d8; S3) 400 mg/m(2) d8 and 30 mg/m(2) d1 and d8. MTD was 500/135 mg/m(2) (S1), 400/40 mg/m(2) (S2), and 500/120 mg/m(2) (S3). Most common dose limiting toxicities were febrile neutropenia, fatigue, and neuromotor toxicities. Most common toxicity was grade 3/4 lymphopenia. Four patients had partial response, 43 patients had stable disease. The RD determined was pemetrexed 500 mg/m(2) (d8) and paclitaxel 90 mg/m(2) (d1 and d8), q21d. The combination was well tolerated and showed efficacy in thyroid carcinoma and mesothelioma.
Hanauske
Axel-R
AR
St. Georg Hospital, Hamburg, Germany. hanauskeax@lilly.com
Dumez
Herlinde
H
Piccart
Martine
M
Yilmaz
Emine
E
Graefe
Tobias
T
Gil
Thierry
T
Simms
Lorinda
L
Musib
Luna
L
Awada
Ahmad
A
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008654:Mesothelioma / Q000188:drug therapy; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D000068437:Pemetrexed; D013964:Thyroid Neoplasms / Q000188:drug therapy; D055815:Young Adult
D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D017239:Paclitaxel